1. Field of the Invention
The present invention relates to methods for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acids (ketorolac) represented by formula (I): ##STR4##
The present invention also relates to novel intermediates useful preparing the 5-aroyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acids (I) and to methods for preparing the novel intermediates.
2. Description of the Background
U.S. Pat. Nos. 4,089,969, 4,344,943, and 4,505,927 disclose 5-aroyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acids. U.S. Pat. No. 4,496,741 discloses a method for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acids by selective decarboxylation. In all these patents, the methods for preparing these compounds are different from those described herein.
U.S. Pat. No. 4,097,579 discloses 5-aroyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acids wherein the benzoyl group is replaced with a pyrrolyl group. U.S. Pat. No. 4,087,539 discloses 5-aroyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acids wherein the benzoyl group is replaced with a furoyl or thienoyl group.
U.S. Pat. No. 4,347,185 discloses a synthesis of 5-benzoyl-7-halo-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylic acid dialkyl diesters by a route different from that described herein, and their subsequent hydrolysis and decarboxylation to 5-benzoyl-7-halo-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids.
U.S. Pat. Nos. 4,347,186 and 4,347,187 discloses a synthesis of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylic acid dialkyl diesters by a route different from that described herein, and their subsequent hydrolysis and decarboxylation to 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids.
U.S. Pat. No. 4,459,759 discloses 5-benzoyl-7-halo-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylic acid dialkyl diesters and dicarboxylic acids.
U.S. Pat. No. 4,873,340 discloses a synthesis of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylic acid dialkyl diesters by a route different from that described herein.
U.S. Pat. No. 4,988,822 discloses intermediates in the synthesis of 5-(substituted aroyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylic acid dialkyl diesters.
U.S. Pat. No. 4,458,081 discloses 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylic acid dialkyl diesters, monoalkyl monoester, and diacids.
U.S. Pat. No. 5,082,950 discloses the preparation of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylic acid dialkyl diesters via the intermolecular free radical coupling of a malonate diester derivative to the 5-position of the 2-aroylpyrrole.
U.S. Pat. No. 5,082,951 discloses the preparation of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-dicarboxylic acid dialkyl diesters via the intramolecular free radical coupling of the corresponding malonate diester derivatives to the 5-position of the 2-aroylpyrrole.
U.S. Pat. Nos. 4,835,288, 4,874,871, 4,353,829, 4,140,698, and 4,849,526 discloses methods for preparing intermediates useful for the synthesis of 5-aroyl-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic acids, the intermediates being different from those described herein.